Genetics Institute, Inc.

Wyeth

Medimmune Limited

The United States of America, as Represented by the Secretary, Department of Health and Human Services

University of Pittsburgh

Beatriz M Carreno

Mary Collins

Gary S Gray

Samuel Goldman

Denise M O'Hara

Maximiliano Vasquez

Geertruida Machteld Veldman

Man Sung Co

Abbie Cheryl Celniker

Andrea Knight

Bonita Rup

Clive R Wood

Laura L Carter

Caroline S Russell

Deborah P Luxenberg

John Edward Andrews

Jason Jussif

Frances K Bennett

Matthew James Whitters

Viia Valge-Archer

Deborah A Young

Naoya Tsurushita

Glenn R Larsen

Paul Robert Hinton

Debra D Donaldson

Katherine Jane Turner

John P Leonard

Marion T Kasaian

Ethan Shevach

Jay Kennedy Kolls

Michelle J Unger

Joann Witek

Michael Chapman Byrne

John Leonard

Vila Valge-Archer

Leslie D Lowe

Kyri Dunussi

Margery Ma

Donna Morris

Florencia Marine McAllister

Rebecca Suzanne McHugh

Padmalatha S Reddy

Geoffrey Laurence Stephens

Caroline Russell

John Andrews

This disclosure provides antibodies and antigen-binding fragments that can act as agonists and/or antagonists of PD-1 (Programmed Death 1), thereby modulating immune responses in general, and those mediated by TcR and CD28, in particular. The disclosed compositions and methods may be used for example, in treating autoimmune diseases, inflammatory disorders, allergies, transplant rejection, cancer, and other immune system disorders.

Nucleic acids encoding antibodies against PD-1

The invention is related to findings that IL-17F-mediated inflammation of airway passages may be mediated via signaling through IL-17R on the basolateral surface of human respiratory epithelial cells. Thus, the present invention provides isolated and purified IL-17F or IL-17R polynucleotides and polypeptides. The present invention also is directed to novel methods for screening test compounds capable of inhibiting, i.e., decreasing, limiting, blocking, or otherwise reducing, IL-17F bioactivity, and methods for diagnosing, prognosing, and monitoring the progress of, disorders related to IL-17F bioactivity, e.g., disorders related to the effects of IL-17F binding to IL-17R on airway inflammation, e.g., in patients with cystic fibrosis, including pulmonary exacerbations due to bacterial infections in same. The present invention is further directed to novel therapeutics and therapeutic targets and to methods for the intervention (treatment) and prevention of said disorders related to IL-17F bioactivity.

Use of IL-17F in diagnosis and therapy of airway inflammation

The invention relates to a humanized anti-B7-2 antibody that comprises a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.

Methods of treatment of autoimmune diseases using humanized immunoglobulin reactive with B7-2

The present invention provides novel isolated and purified polynucleotides and polypeptides related to a novel ligand for glucocorticoid-induced TNF receptor (GITR). The invention also provides antibodies to the GITR ligand (GITRL). The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating disorders arising from disregulation of the immune system (e.g., autoimmune disorders, inflammatory diseases, and transplant rejection, and cancers and infectious diseases) using GITRL and/or modulators of GITRL. The present invention is further directed to novel therapeutics and therapeutic targets and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of said disorders arising from disregulation of the immune system, as related to GITRL and GITR.

Method of treating or ameliorating an immune cell associated pathology using GITR ligand antibodies

The invention relates to humanized anti-B7-2 and anti-B7-1 antibodies, wherein each comprise a variable region of non-human origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.

Methods for modulation of immune responses using humanized immunoglobulins reactive with B7-1 molecules

Methods of upmodulating adaptive immune response using anti-PD-1 antibodies

Antibodies against PD-1

Methods and compositions for modulating interleukin-21 (IL-21)/IL-21 receptor (MU-1) activity using agonists or antagonists of IL-21 or IL-21 receptor ('IL-21R' or 'MU-1'), are disclosed. IL-21/IL-21R antagonists can be used to induce immune suppression in vivo, e.g., for treating or preventing immune cell-associated pathologies (e.g., pathologies associated with aberrant activity of one or more of mature T cells (mature CD8+, mature CD4+ T cells), mature NK cells, B cells, macrophages and megakaryocytes, including transplant rejection and autoimmune disorders). IL-21/IL-21R agonists can be used by themselves or in combination with an antigen, e.g., as an adjuvant (e.g., a vaccine adjuvant), to up-regulate an immune response in vivo, e.g., for example, for use in treating cancer and infectious disorders.

Methods and compositions for modulating interleukin-21 receptor activity

The invention provides an antibody-toxic moiety conjugates comprising an antibody that specifically recognizes a molecule expressed on the surface of a T cell which is expressed only on T cells and is only expressed transiently on T cells upon T cell activation. Preferably, the T cell molecule is CTLA4. The invention further provides anti-CTLA4 antibodies and humanized forms thereof.

Antibodies against CTLA4

Disclosed are methods for downmodulating an immune response comprising contacting an immune cell with an agent that modulates the interaction between PD-1 and a PD-1 ligand (e.g., soluble forms of PD-1 or PD-1 ligand or antibodies to PD-1) to thereby modulate the immune response.

Methods for downmodulating immune cells using an antibody to PD-1

Method of transplanting cells by contacting donor cells with B7-1-and B7-2-specific immunoglobulins

Humanized immunoglobulin reactive with B7-2 and methods of treatment therewith

Humanized immunoglobulin reactive with B7 therewith

Humanized immunoglobulin reactive with b7-2 and methods of treatment therewith

Growing community of inventors

Acton, MA, United States of America

Beatriz M Carreno